The simple thinking behind great manuscripts

December 1, 2016

Dr. Janice Nigro, Filipodia Editor

My career has been focused on the genetics of cancer development. If you had told me this back when I started graduate school, though, I would have said, “No way!” At the time, I was interested in model organisms to study disease. But circumstances changed, and there I was interviewing with a potential PhD advisor who studied cancer. I was bold enough to tell him my concerns; I was not interested in cancer research because the field seemed too competitive, especially for a graduate student. He had a simple answer for me, “You have to find your niche.” In the cancer field, where up to that point the emphasis had been on rodent models, his niche was primary human tumors.

He made me see a simple solution to what was a highly complex disease as well as field of study. That statement convinced me that above all else he would teach me how to be a good scientist. And that was my answer when he asked why I wanted to be in his lab. His question, “What are the genetic mutations driving cancer?” never quit on him. He was not just thinking about what was going to happen today or tomorrow or in the next 6 months, but what was going to drive his entire career. That is what we are talking about when someone has vision.

Lesson 1 in career development and publishing papers: ask the kind of question where the answers lead to more questions.

My graduate experience turned me onto the study of cancer and moreover convinced me to continue with a career in science. Eventually, I would have to leave the lab, though, and I too would have to find my own niche.

I continued working in labs as a postdoc where the focus was cancer, but it wasn’t until I met a neuropathologist that I found a niche within the realm of human tumors that really turned me on. At the time, the genetic changes occurring in human brain tumors had not been well-defined, and I suddenly saw clearly how my training as a PhD might uniquely impact clinical science.

I became interested in a specific subset of adult brain tumors-low grade gliomas-a sort of niche within a niche. Not much was known about them except that patients lived with their disease longer than those with a more aggressive brain tumor type, glioblastoma multiforme. When I attended my first medical conference devoted to brain tumors, I was completely convinced that the field needed a stronger basic science perspective. It was a plus that it was a small field of study.

I found my niche, although it took me a few years, and it was unexpected. My mistake for most of my postdoc had been to do what I thought I should do rather than what I wanted to do.

Lesson 2 in career development and publishing papers: follow your heart (it sounds cliché but it’s the truth).

I always thought of cancer as a model system to identify critical genes, not only for the disease itself, but for understanding biology in general. Cancer to me was like selected yeast genetic mutants, harboring the kinds of mutations in genes that might reveal some new biological insight. So I thought I could find interesting genes to look at in human gliomas and then perhaps go on to learn about their roles in brain or neuronal development.

I finally started to gain momentum in achieving that goal of making an impact on the field in my own way, but in another country (Norway if you have not read my previous post). Unfortunately, although my project was novel and timely, I never published enough. If you were counting papers, then yes I never published enough; if you were counting citations of papers and the concepts presented, then probably no.

And therein lies the problem for today’s scientists. “You need papers” is what we hear, instead of “What do you need to really make something happen?”

My story took an abrupt ending. Geography and culture influenced my decision. To some degree, I had contributed to work my whole career that was beyond my wildest dreams. I furthermore felt vindicated for choosing my program of study when other labs identified a mutation in low grade gliomas-a relatively rare type of tumor-that led to a groundbreaking discovery in our understanding of the corruption of pathways leading to cancer. It took all sorts of experts to put that story together.

Lesson 3 in career development and publishing papers: it’s impossible to identify the exact projects or disciplines that will yield the greatest breakthroughs in science.

We think cancer is important because it’s a disease, and one that affects essentially all of us somehow. But how far would we have gotten without some of our insights that come from yeast or drosophila? Or who knows, that symbiotic relationship between a squid and bacteria? Some things are just interesting to know.

Today we have this insatiable desire to have things now. Make ourselves accountable. Biology does not work this way. Or at least not for me. I thought a lot about the value of slow cooking science projects when I visited an estate in Modena, Italy where the owners produce traditional balsamic vinegar. Traditional balsamic vinegar must be aged a minimum of 12 years, and it goes on up from there (even to > 100 years). But even before you get to start the production of the vinegar, you must have the grapes to do so. Vineyards take years to develop as well so there is a significant time investment before you even make your first bottle, if you start from nothing. The owner said, “You can only do it if you truly have a passion for it.”

At the end of my visit at Acetaia Villa di San Donnino, I couldn’t help but feel the parallels to biological science today. I wondered what kind of impression a trip to the estate would make on a committee from the NIH. Are three-year grants really sufficient to evaluate the potential of a project or the scientist running it? Some things are worth waiting for.

Lesson 4 in career development and publishing papers: the most interesting concepts don’t develop overnight.

Some of our actions today seem to be working against these principles and potentially scientific progress. No doubt some amazing discoveries are being made, but are we losing some in our overzealous critique of each other’s progress? For one, we are too caught up with trends. And who decides what the trends should be and why? In the early 90s, we started the trend of translational science, and now we are writing that we need to go back to basics [1]. Meanwhile other countries are caught up in the translational mania. Second, we are stuck on accountability. Having many papers might be significant, but it also might not be. The slow cooking project might need more time to reach that point where there is no stopping it. But prior to that point, we are cutting off the gas before it’s cooked. Finally, we have turned science into a competition and run it like a business. A certain number of people and money are necessary to run a good lab, but after that it’s a bit about ego-chasing. Some labs simply do not need more money to run effectively, for example.

Productivity thus is not necessarily about numbers; it’s really about impact.

Lesson 5 in career development and publishing papers: impact on a field supersedes all other numbers.

Some of our foremost leaders are expressing concern with the current culture [1,2,3]. I would suggest that worldwide we initiate change by doing something simple-be reasonable. Some of the decisions made in academic departments and review committees defy logic. We have to ask ourselves whether we are acting responsibly and respectfully towards our trainees and colleagues-not just the ones who look or think like us.

We don’t question art. It just is. Too much management in terms of accountability is in direct opposition to our training, which in some respects is as Captain Kirk says, “To boldly go where no man has gone before.” Maybe social media could teach us a lesson. If you can clearly state your idea and the long term implications in 140 characters or less, you probably have something worth working on.